Tumor-associated antigens serve as potential targets for the immune system of the host and may play a role in establishing the malignant phenotype of the tumor cell. The long-term objective of the proposed research is to understand the genetic and epigenetic mechanisms by which the tumor cell regulates expression of its tumor-associated antigens. Antigenic variants of murine lymphomas growing in tissue culture will be used to study the genetics of several model normal and tumor-associated cell surface antigens. Somatic genetic analysis will be used to establish the number, dominance, and nature (structural or regulatory) of genes involved in antigen biosynthesis. Mutants which have been characterized genetically will be used in collaborative biochemical studies to build up a picture of the steps in antigen biosynthesis and its control. These studies, which have already been initiated, will be continued using the Thy-1 antigen as a model normal cell surface differentiation alloantigen and the TL antigen as a model tumor-associated antigen. Studies on dimethylbenzanthracene-induced murine lymphomas will be undertaken to extend the analysis to the unique tumor-associated antigens of chemically induced tumors.